12. Tetracyclines and glycylcyclines Flashcards
List the Glycylcyclines.
- Tigecycline
List the short DOA Tetracyclines.
- Tetracycline
- Oxytetracycline
List the long DOA Tetracyclines.
- Doxycycline
- (Minocycline)
How long is the DOA of short acting tetracyclines?
6-8 hrs
How long is the DOA of long acting tetracyclines?
16-18hrs
What is the MOA of Tetracyclines?
Tetracyclines reversibly bind 30s subunit → block tRNA binding + stop peptide formation. They are broad-spectrum but bacteriostatic only.
What spectrum does Tetracyclines cover?
Gram +/- anaerobes and aerobes; intracellular pathogens:
- H. influenza is very susceptible
- Good effect for Rickettsia strains, Mycoplasma, Chlamydia, Legionella
- but not first choice b/c fluoroquinolones + macrolides are better tolerated
- Also good for T. pallidum, Actinomyces, Borrelia, Brucella and Francisella, P. falciparum, Leptospira, H. pylori, Yersinia and V. cholerae
- Can be effective against Staph (including some MRSA), Strep, Pneumococci but ~40% are resistant
- KES group - can be effective but 30-40% resistant
- Pseudomonas, Acinetobacter and Gonococci are totally resistant
What is the possible resistance mechanism against Tetracyclines?
Mostly via efflux pumps.
How are the kinetics like for Tetracyclines?
- Given orally
- Bind to + chelate any multivalent cations (Fe, Ca, Mg) → ↓ absorption of both the cations and the tetracyclines
- Good distribution, but NO CNS ENTRY
- Excretion mainly by urine (small % by bile) (sketchy says mostly by bile/GI)
- Doxycycline can be well eliminated by active biliary transport in renal failure.
What are the indications for Tetracyclines?
Better drugs exist for most of the tetracyclines’ spectrum, but still some specific indications.
- Atypical pneumonia - via Chlamydia or Mycoplasma; doxycycline as an alternative if macrolides / fluoroquinolones ineffective
- STDs: from Chlamydia, Ureaplasma causing urethritis, cervicitis or PID
- Prostatitis
- Rickettsia: only in patients above 9 (due to chelation issues)
- Brucellosis / Tularemia in combo with streptomycin
- Early Lyme Borreliosis
- Malaria via P. falciparum - in acute complicated phase (parasitemia > 5% and organ failures), doxycycline can be part of combination therapy. Doxycycline can be given alone as malarial prophylaxis (but causes photosensitivity)
What are the side effects of Tetracyclines?
- Bone / tooth malformations - via Ca/Fe/Mg chelation; deposits in fetal bone causing deformity → contraindicated in pregnancy.
- Hepatotoxicity - at total dose > 4 g, liver necrosis may develop.
- Renal Tubular Acidosis - especially in expired meds; type 2 or “Fanconi syndrome”
- Vestibular reactions
- Photosensitivity
- GI effects - common; alter normal flora → candidiasis or C. diff colitis
What is the MOA of Glycylcyclines?
There is only one Glycylcyline which is Tigecycline. It is related to tetracyclines and binds 30s ribosomal subunit.
What are the side effects of Glycylcyclines?
- GI effects - most common
- Injection site pain and hepatitis / jaundice, less common
What are the indications for Glycylcyclines?
- Main use is for VRE / MRSA.
- Complicated Skin/Organ Infections - Staph, Strep, Enterococcus
- Intra-abdominal/Wound infections - B. fragilis, E. coli, C. perfringens
- Community-Acquired Pneumonia - S. pneumo, H. flu and Legionella
What spectrum does glycylcyclines cover?
Broad spectrum against both Gram + and Gram -
- Staph, Strep and Enterococcus including VRE and some MRSA
- E. coli, Klebsiella, Enterobacter, B. fragilis, C. perfringens
- H. flu and Legionella.
